Klk1 as one of the genes contributing to hypertension in Dahl salt-sensitive rat
Klk1 as one of the genes contributing to hypertension in Dahl salt-sensitive rat
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DOI：
10.1161/01.hyp.0000161969.65767.0d
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发表时间：
2005-05-01
期刊：
影响因子：
8.3
通讯作者：
Sumiya, H
中科院分区：
文献类型：
--
作者：
Iwai, N;Yasui, N;Sumiya, H
对来自Dahl盐敏感大鼠和Lewis大鼠的107只雄性F-2大鼠的血压进行了全基因组数量性状基因座分析。血压通过遥测进行评估，并使用>；400微卫星标记进行基因分型。在1号染色体和10号染色体上发现了两个影响血压的主要数量性状基因座。RT-PCR检测了染色体1数量性状基因座周围的366个转录本的表达水平，发现Dahl盐敏感大鼠肾脏中Klk1(激肽释放酶1)和Ngfg(神经生长因子γ)的mRNA水平显著低于Lewis大鼠。与Lewis大鼠相比，Dahl盐敏感大鼠的激肽释放酶1蛋白表达水平也受到抑制。由于激肽释放酶-激动素系统已被证明参与肾功能，包括盐的动态平衡，很可能Klk1的表达减少导致Dahl盐敏感型大鼠的盐敏性高血压。
A genome-wide quantitative trait loci analysis for blood pressure was performed using 107 male F-2 rats derived from Dahl salt-sensitive and Lewis rats. Blood pressure was assessed by telemetry, and >400 microsatellite markers were used for genotyping. Two major quantitative trait loci for blood pressure were identified at chromosome 1 and chromosome 10. The expression levels of 366 transcripts around the chromosome 1 quantitative trait loci were assessed by RT-PCR, and we found that the Klk1 ( kallikrein 1) and Ngfg ( nerve growth factor gamma) mRNA levels were significantly reduced in the kidneys of Dahl salt-sensitive rats compared with those in Lewis rats. The expression levels of kallikrein 1 protein were also suppressed in Dahl salt-sensitive rats compared with those in Lewis rats. Because the kallikrein-kinin system has been shown to be involved in renal function, including salt homeostasis, it is likely that the reduced expression of Klk1 contributes to salt-sensitive hypertension in Dahl salt-sensitive rats.